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Bovine Spongiform Encephalopathy: An Update

Bovine Spongiform Encephalopathy: An Update . Linda A.Detwiler Senior Staff Veterinarian USDA, APHIS, VS. Transmissible Spongiform Encephalopathies. prolonged incubation period progressive debilitating neurological illness pathological changes confined to CNS fatal.

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Bovine Spongiform Encephalopathy: An Update

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  1. Bovine Spongiform Encephalopathy: An Update Linda A.Detwiler Senior Staff Veterinarian USDA, APHIS, VS

  2. Transmissible Spongiform Encephalopathies • prolonged incubation period • progressive debilitating neurological illness • pathological changes confined to CNS • fatal

  3. Transmissible Spongiform Encephalopathies • Scrapie Associated Fibrils (SAF) - negative stain EM • Transmissibility

  4. Transmissible Spongiform Encephalopathies: Etiology • agent not fully characterized • smaller than smallest known virus • ellicits no detectable immune or inflammatory response in the host • resistant to most disinfectants and treatments which normally destroy nucleic acids

  5. Transmissible Spongiform Encephalopathies: Agent Theories • VIRUS - unconventional, unusual biochemical and biopysical properties • VIRINO - host-derived protein coat coupled to a small noncoding regulatory nucleic acid • PRION - host-coded normal cellular protein becomes partially protease resistant through post tranlational conformation change

  6. Transmissible Spongiform Encephalopathies: Human • Creutzfeldt-Jakob Disease (CJD) • Gerstmann-Straussler-Scheinker syndrome (GSS) • fatal familial insomnia (FFI) • Kuru • variant CJD (vCJD)

  7. Transmissible Spongiform Encephalopathies: Scrapie • Reported most sheep producing regions • Known over 250 years • Sheep, goats, moufflon

  8. Transmissible Spongiform Encephalopathies: Chronic Wasting Disease • First recognized as disease syndrome - 1967 • Colorado, Wyoming - endemic areas • Farm raised elk

  9. Transmissible Spongiform Encephalopathies: Transmissible Mink Encephalopathy • Affects ranch raised mink • First recognized in 1947 • Detected and documented in Canada, Finland, (East) Germany, Russia • Associated with feed

  10. Transmissible Spongiform Encephalopathies: Animal • Bovine Spongiform Encephalopathy • Feline Spongiform Encephalopathy • TSE of Exotic Ruminants

  11. Distribution of Infectivity spinal cord dorsal root ganglia brain trigeminal ganglia bone marrow distal ileum

  12. Transmission

  13. BSE Diagnostics • No live animal test • No preclinical test • Need brain tissue • Histology, IHC, WB, ELISA • "Negatives" do not guarantee absence of infectivity

  14. TSE Diagnostics: EU Approved • Histology • Standard IHC and Western Blot • Prionics AG - modified Western Blot (8 hrs) • Enfer Ltd. - High throughput chemiluminescent ELISA (3-4 hrs) • CEA - Sandwich Immunoassay (3-4 hrs) • all require brain/clinical cases

  15. BSE STATISTICS for GREAT BRITAIN* (as of February 9, 2001) Total number of confirmed cases: 177,717 Total number of affected herds: 35,150 Proportion of dairy herds affected: 61.3% Proportion of beef suckler herds affected: 16.6% Confirmed total herd incidence: 37.5% * England, Scotland, Wales

  16. Confirmed cases of BSE in Great Britain by year of restriction (1986 - 1 December 2000)* *Includes 46 cases not subject to official restriction and identified by proactive surveillance or at autopsy.

  17. UK MAFF Actions • Mammalian to food animal feed ban • Over thirty month scheme • Selective Cull • Offspring Cull • SRM/SBO bans • Beef on the bone prohibition - No longer in place

  18. 86 First cases of BSE Total number of cases (3-12-01) UK >180,000 Belgium - 23 Ireland -653 Spain - 32 Italy - 4 Portugal - 528 Netherlands - 13 Switzerland - 370 Liechtenstein - 2 France - 279 Denmark - 2 Germany - 44 Luxembourg - 1 00 Denmark Germany Spain Portugal Switzerland Netherlands Belgium Luxembourg France Ireland Italy 90 94 97

  19. BSE Incidence Rate (per million cattle > 2 yrs) 9899 United Kingdom 596 422 Portugal 147 236 Switzerland 16 53 Ireland 22 27 France 2 3 Belgium 4 2 Netherlands 1 1

  20. BSE: Control Measures in EU • SRM bans on sheep, goats, cattle (Oct 2000) • Prohibit feeding of most processed animal proteins (excluded fish meal) to farmed animals (Jan 2001) • test of all cattle >30months at slaughter (if cannot test destroy) (Jan 2001)

  21. EU BSE Surveillance • CNS cases • Fallen stock and emergency slaughter • herdmates of positive cases in some countries • all bovines to slaughter > 30 months of age or older • Negative doesn't guarantee lack of infectivity

  22. BSE: Comparison of surveillance • France • 450,000 > 30 mos tested - 10 pos (1-01 to 3-01) • 54,000 fallen stock tested - 68 pos (summer 2000 to 3-01) • Switzerland • 14,900 normal slaughter - (3 pos 99; 0 pos 00) • 22,900 fallen and ES - (22 pos 99; 16 pos 00)

  23. Fallout from BSE (Nov-Feb) • Meat sales drop dramatically • Loss of consumer confidence • Politicians resign or lose jobs • Disposal Problems (carcasses/MBM) • Logistical test problems

  24. EU Geographical BSE Risk • 25+ countries evaluated • Member states • Non member states • Examined: • Challenges • Stability of system

  25. EU Geographical BSE Risk • Challenges • External • cattle • MBM • Internal • cattle • MBM

  26. EU Geographical BSE Risk (continued) • Stability • Feed bans • Rendering • Time • Temperature • Pressure • SRM bans

  27. EU Categories of Risk • I - Highly Unlikely • II - Unlikely but Cannot be excluded • III - • Likely but not confirmed • BSE confirmed at a lower level • IV - BSE confirmed at a higher level

  28. Category I • Argentina • Australia • Chile • New Zealand • Norway • Paraguay • Uruguay • Botswana • Namibia • Nicaragua, • Swaziland

  29. Category II • Austria • Finland • Sweden • Canada • United States

  30. Category III • Germany • Italy • Spain • Lithuania • Belgium • Denmark • France • Ireland • Luxembourg • Netherlands • Switzerland

  31. Category IV • United Kingdom • Portugal

  32. CJD vs. vCJD • sporadic, genetic, iatrogenic • 55-75 yrs of age • < 6 mos clinical course • memory loss, myoclonus, dementa • no plaques in brain • food contaminated with BSE infected CNS • 28 yrs. median • avg 14 mos clinical course • psychiatric followed by neuro • florid plaques

  33. vCJD Cases (as of April 2001) * vCJD cases - 98 definite and probable * vCJD cases - 2 definite, 1 probable

  34. vCJD cases by Year

  35. ? vCJD = BSE epidemiology macaques glycoform patterns strain-typing transgenetic studies

  36. vCJD: Distribution of Infectivity • Different than classical CJD • Spleen, tonsil, appendix • Retrospective study - 3000 samples - negative results • leucodepletion of blood supply • UK imports plasma and plasma products • US and Canadian deferrals

  37. USDA ACTIONS: Prevention and Surveillance • Import Regulations • Surveillance • Formal Risk Assessments • TSE Working Group

  38. BSE - Prevention • Import Restrictions - countries with BSE • July 1989 - live ruminants • November 1989 - ruminant products • 1991 - formal regulations • Import Restrictions - Europe • December 1997 • January 1998 - interim rule • all live ruminants and most ruminant products

  39. BSE - Prevention • Import Restrictions - Europe • December 6, 2000 - all MBM, etc. regardless of species • Evaluations of other countries • South America underway • Central America • Asia

  40. Import Policies and Regulations • North American Policy

  41. USDA ACTIONS: Surveillance • Field CNS Cases • VDL data • CNS condemns at slaughter • "Downers"

  42. BSE Surveillance: Total Bovine Brain Submission by State May 10, 1990 thru March 31, 2001 71 35 VT-96 213 42 226 63 NH-14 266 474 217 467 MA- 35 117 55 1255 CT- 19 89 353 2 187 137 16 79 NJ-320 43 186 156 49 1540 127 DE-2 1502 157 MD-22 51 196 221 65 44 25 13 220 5 310 2212 143 182 17 Total = 12,341 Source: USDA, APHIS,NVSL Note: None of the US Brain Submission Have Tested Positive for BSE

  43. BSE Surveillance NVSL Bovine Brain Submissions FY 93-99 982 988 842 855 Total Submissions 731 729 Tested by IHC 651 Downers (fallen stock) 495 584 465 412 388 344 168 219 112 266 223 199

  44. NVSL BSE Surveillance Bovine Brain Submissions FY 00-01 (as of 3-31-01) 2309 2135 Total Submissions 1895 Tested by IHC "Downers" (fallen stock) 713 643 548

  45. US Surveillance: Current Direction • Regional Goals

  46. US Regions for BSE Surveillance NW NC NE C SW E SE SC

  47. US Regional Goals for BSE Surveillance - FY 2001 564 606 462 466 766 312 644 734

  48. US Regional Goals for BSE Surveillance (2001) REGION GOAL 2x OIE goals FY 99 FY 2000 FY 2001* NW 564 27 134 118 SW 466 256 226 68 C 766 159 120 60 SC 734 281 1094 250 NC 606 135 240 54 NE 462 331 461 122 E 312 26 30 16 SE 644 194 367 51 * as of March 31, 2001

  49. Increase of submissions • Down cattle: • aged; dairy vs. beef • condemns at slaughter • 3D/4D • Renderers • Remind VDLs to submit data

  50. Surveillance Reminders • Submissions need: • obex • age of bovine • ID • clinical signs (or down) • 10-4 & supplemental • plant number • Questions call NVSL (515-663-7521)

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